gedivumab (RG7745) / Roche - LARVOL DELTA

Nonclinical Investigation of the Potential of MHAA4549A, an Anti-Influenza A Therapeutic Antibody, to Mediate Antibody-Dependent Enhancement. (PubMed, Toxicol Sci) - "In a mouse model of X31 infection, intravenous administration of MHAA4549A resulted in delayed body weight recovery, but no exacerbation in orthogonal endpoints including mortality, lung viral titers or genomes, lung weights, or severity of influenza pneumonia. Overall, the totality of nonclinical data did not demonstrate any clear indication of ADE of infection at non-neutralizing concentrations, suggesting a low risk for MHAA4549A to cause enhanced influenza A-mediated disease at sub-therapeutic doses."

Journal • Infectious Disease • Influenza • Pneumonia • Respiratory Diseases

Administration of rAAV Encoding Monoclonal Antibodies Protects Mice Challenged with a Lethal Dose of H3N2 Influenza Virus and Neutralizes H1 and H3 Strains. (PubMed, Acta Naturae) - "Administration of rAAV-C585, rAAV-MHAA4549A, and rAAV-1G01 conferred 100% protection to mice challenged with a lethal dose of the H3N2 influenza virus. The efficacy of rAAV-CR9114 and rAAV-MEDI8852 against this influenza virus strain was lower, at 80 and 75%, respectively."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases

Monoclonal antibodies against influenza viruses: a clinical trials review. (PubMed, Front Immunol) - "MHAA4549A demonstrated a 97.5% reduction in viral load in H3N2 models and showed synergistic effects with oseltamivir in severe cases. However, despite preclinical promise, others, such as VIR-2482 (intramuscular) and MEDI8852, failed in Phase 2 trials...mAbs hold promise for high-risk groups and pandemics but require further engineering to enhance efficacy and overcome biological barriers. Refinements in administration and design could establish monoclonal antibodies (mAbs) as a key tool in the management of influenza."

Journal • Review • Gastrointestinal Disorder • Infectious Disease • Influenza • Pain • Respiratory Diseases

Polyclonal and Monoclonal Antibodies for the Treatment and Prevention of Influenza. (PubMed, J Infect Dis) - "The COVID-19 pandemic demonstrated that these approaches, especially monoclonal antibodies, may have unique potential in certain stages of disease and populations, especially in preventing severe disease in a population without preexisting immunity or in those with a limited capacity to mount an effective humoral immune response. This review summarizes past and ongoing efforts in using monoclonal and polyclonal antibodies for the treatment and prevention of influenza, focusing on products that have entered clinical trials and drawing lessons from COVID-19 to direct future efforts on these strategies."

Journal • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of the Monoclonal Antibody MHAA4549A in Patients With Acute Uncomplicated Influenza A Infection. (PubMed, Open Forum Infect Dis) - "Between the MHAA4549A and placebo groups, no statistically significant differences occurred in the median time to alleviation of all symptoms, nasopharyngeal viral load, or duration of viral shedding. While MHAA4549A was safe and well tolerated with confirmed exposure, the antibody did not improve clinical outcomes in patients with acute uncomplicated influenza A infection."

Clinical • Journal • P2 data • Infectious Disease • Respiratory Diseases

Pharmacokinetics of the Monoclonal Antibody MHAA4549A Administered in Combination With Oseltamivir in Patients Hospitalized With Severe Influenza A Infection. (PubMed, J Clin Pharmacol) - "MHAA4549A detection in tracheal aspirate samples indicated exposure in the lower respiratory tract. Oseltamivir and oseltamivir carboxylate exposures were similar between MHAA4549A-treated and placebo groups, suggesting a lack of MHAA4549A interference with oseltamivir pharmacokinetics."

Clinical • Combination therapy • Journal • PK/PD data • Infectious Disease

Advances in respiratory virus therapeutics - A meeting report from the 6th isirv Antiviral Group conference. (PubMed, Antiviral Res) - "Updates were presented on several influenza antivirals including baloxavir, CC-42344, VIS410, immunoglobulin, immune plasma, MHAA4549A, pimodivir (JNJ-63623872), umifenovir, and HA minibinders; RSV antivirals including presatovir (GS-5806), ziresovir (AK0529), lumicitabine (ALS-008176), JNJ-53718678, JNJ-64417184, and EDP-938; broad spectrum antivirals such as favipiravir, VH244, remdesivir, and EIDD-1931/EIDD-2801; and host directed strategies including nitazoxanide, eritoran, and diltiazem. Other topics included considerations of novel endpoints such as ordinal scales and patient reported outcomes (PRO), and study design issues, and other regulatory considerations for antiviral drug development. The aim of this report is to provide a summary of the presentations given at this meeting."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

A phase 2 randomized, double-blind, placebo-controlled trial of MHAA4549A, a monoclonal antibody, plus oseltamivir in patients hospitalized with severe influenza A infection. (PubMed, Antimicrob Agents Chemother) - "Variability in patient removal from oxygen supplementation limited the utility of the primary endpoint. Validated endpoints are needed to assess novel treatments for severe influenza A."

Clinical • Journal • P2 data • Immunology • Infectious Disease

Pharmacokinetics of MHAA4549A, an Anti-Influenza A Monoclonal Antibody, in Healthy Subjects Challenged with Influenza A Virus in a Phase IIa Randomized Trial. (PubMed, Clin Pharmacokinet) - P2a; "MHAA4549A serum PKs were consistent with that of a human IgG1antibody without known endogenous targets. MHAA4549A showed nonlinear PKs in nasopharyngeal swab samples, which will guide future dose selection to achieve the high drug concentrations needed at the site of action for efficacy. These data demonstrate no PK interactions between MHAA4549A and oseltamivir, and support flat dosing."

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